Article pubs.acs.org/ac
Direct Ionization of Solid-Phase Microextraction Fibers for Quantitative Drug Bioanalysis: From Peripheral Circulation to Mass Spectrometry Detection Sheelan Ahmad,*,†,§ Michael Tucker,‡ Neil Spooner,† Darragh Murnane,§ and Ute Gerhard§ †
Bioanalytical Science and Toxicokinetics, Drug Metabolism and Pharmacokinetics, GlaxoSmithKline Research and Development, Ware, Hertfordshire SG12 0DJ, U.K. ‡ MGT Systems, Chapel Lane, East Bridge, Suffolk, IP16 4SG, U.K. § School of Life and Medical Sciences, Department of Pharmacy, University of Hertfordshire, Hatfield, Hertfordshire AL10 9AB, U.K. S Supporting Information *
ABSTRACT: A novel approach is described for the quantitative bioanalysis of drugs in blood samples by ionization of the analytes collected on solid-phase microextraction (SPME) fibers by mass spectrometry (MS). The technique combines the attractive features of SPME microsampling using minimal sample volumes with the speed, selectivity, and sensitivity capabilities of MS detection. The method reported in this study involved generating gas-phase ions directly from SPME fibers without the need for any additional sample preparation or chromatographic separation; the entire process was completed within 5 min. Traditionally, analytes extracted by SPME fibers are desorbed by washing with suitable solvents followed by a transfer into a sample vial and subsequent liquid chromatography−tandem mass spectrometry (LC−MS/MS) analysis to quantify the amount of analyte extracted and thereby determining the analyte concentration in the matrix. These sample preparation steps are completely eliminated by inserting the SPME fiber directly into the MS. Physiologically relevant concentrations of metoprolol and propranolol in blood samples were measured over several orders of magnitude down to concentration levels of 10 ng/mL. This preliminary assessment of direct SPME−MS showed high sensitivity (ng/mL), acceptable reproducibility (30 μL/min) resulted in excess solvent forming larger droplets that ultimately compromised the shape and efficiency of the cone jet and in turn impacted the quality of spectrum obtained. A poor performance was also observed with lower solvent flow rates (
